Vulvodynia (VVD) is debilitating chronic vulvar pain that occurs in the absence of visible findings or clinically identifiable neurological disease. Between 2000 and 2005, we estimated the prevalence ofvulvodynia and examined factors associated with its largely unknown etiology (NIH-ROI-HD38428). We learned that nearly 16% of reproductive aged women self-report current or past history of vulvar pain lasting >3 months (an estimated 14 million U.S. women annually), less than 50% seek treatment, few receive an adequate diagnosis, and Hispanic women are more likely to report vulvar pain. Regarding etiology, we learned that women with VVD compared to controls have a) higher levels of neurogenic inflammation markers, b) more psychological trauma and psychiatric morbidity antecedent to vulvar pain symptoms, c) a more prevalent history of environmental exposures that act on immuno-inflammatory response (IIR), and d) significant abnormalities in the characteristics of their vaginal microflora. Furthermore, recent studies have suggested that women with VVD may have an alteration in genes that regulate cytokine expression. Collectively, these findings suggest that VVD is the result oran altered IIR mechanism that occurs as a consequence orreproductive, gynecologic, environmental, or psychological exposures, with abnormal vaginal microflora and genetic polymorphisms as potential modifiers o[the effects o{interest. To test this etiological hypothesis we propose to screen a multiracial sample of approximately 24,000 women from the administrative databases of 4 community health clinics that closely resembles the surrounding general population. Through screening procedures, we expect to identify 325 women with VVD who mayor may not have been previously diagnosed. After clinicalconfirmation, these cases will be frequency-matched to 325 randomly-sampled controls. Data collection and analyses will determine I) whether reproductive, gynecological and environmental exposures influence the odds ofVVD, 2) whether psychological trauma and psychiatric morbidity influence the odds ofVVD, and 3) whether markers of immuno-inflammation and nerve fiber proliferation are directly associated with the odds ofVVD, and the extent to which genetic and microbiological markers modify associations in I and 2 above. A recent congressional report has cited the need for new educational initiatives to create more awareness of VVD, but the repolt also indicates that the ability to implement improved treatment and prevention strategies hinges on our understanding ofVVD etiology. Our proposed study is unique in that it uses an epidemiological approach with adequate statistical power to confirm specific antecedent risk factors among a diverse sample of women at risk ofVVD (who mayor may not have sought care for their condition), while also measuring biological markers and related psychological processes that inform the plausibility of potential etiological pathways. We have also built into our study sophisticated analytical techniques to address the extent to which biases inherent in observational case-control studies could potentially influence our associations. Three important enhanced research goals have been added to be accomplished during the first 2 years of this study. We will determine I) whether demographic characteristics of women identified through community clinic-based administrative databases are comparable to that of census data drawn from the general population surrounding the community clinic, 2) whether the prevalence of vulvar pain symptoms in a sample of women derived from community clinic-based administrative databases that includes insured and uninsured subjects is comparable to that of similarly aged women sampled through a true population-based assessment done in the Boston Metropolitan Area, and 3) what factors contribute toward women choosing to or not choosing to palticipate in studies that involved stigmatizing conditions such as vulvodynia. These enhanced research aims have enormous impact on all scientists involved in population-based studies that previously used approaches such as random digit dialing and motor vehicle registration directories that are now no long viable for identifying population-based subjects. It will also help determine what factors contribute toward successful recruitment of subjects for important studies of stigmatizing conditions which can be extremely prevalent among women.